Treatment failure in children in a randomized clinical trial with 10 and 20 days of meglumine antimonate for cutaneous leishmaniasis due to Leishmania viannia species.

Clinical response to supervised treatment of Colombian patients with cutaneous leishmaniasis was evaluated in a randomized controlled trial comparing 10 days versus 20 days of treatment with meglumine antimonate (20 mg Sb/kg/day). Masked examiners evaluated clinical response defined as 100% re-epithelialization of all lesions at 13 weeks and no relapses during 52 weeks of follow-up. The efficacy of meglumine antimonate for 10 days' treatment was 61% (28 of 46) compared to 67% (24 of 36) for 20 days. There was a significantly lower clinical response for children < 5 years in both 10-day (11%) and 20-day (25%) groups compared to patients aged 5-14 years (67% and 75%, respectively) and 15 years or more (81% and 83%, respectively). Overall efficacy of treatment schedules was comparable, but lower than expected, mainly because of low efficacy in children. Pathogenicity of infection and pharmacokinetics may affect the treatment response in children. New therapeutic alternatives should be evaluated in trials that include children and women.

Positive IgG Western blot for Borrelia burgdorferi in Colombia.

In order to evaluate the presence of specific IgG antibodies to Borrelia burgdorferi in patients with clinical manifestations associated with Lyme borreliosis in Cali, Colombia, 20 serum samples from patients with dermatologic signs, one cerebrospinal fluid (CSF) sample from a patient with chronic neurologic and arthritic manifestations, and twelve serum samples from individuals without clinical signs associated with Lyme borreliosis were analyzed by IgG Western blot. The results were interpreted following the recommendations of the Centers for Diseases Control and Prevention (CDC) for IgG Western blots. Four samples fulfilled the CDC criteria: two serum specimens from patients with morphea (localized scleroderma), the CSF from the patient with neurologic and arthritic manifestations, and one of the controls. Interpretation of positive serology for Lyme disease in non-endemic countries must be cautious. However these results suggest that the putative "Lyme-like" disease may correlate with positivity on Western blots, thus raising the possibility that a spirochete genospecies distinct from B. burgdorferi sensu stricto, or a Borrelia species other than B. burgdorferi sensu lato is the causative agent. Future work will focus on a survey of the local tick and rodent population for evidence of spirochete species that could be incriminated as the etiologic agent.

Lack of an association between the ASN-108 mutation in the dihydrofolate reductase gene and in vivo resistance to sulfadoxine/pyrimethamine in Plasmodium falciparum.

Sulfadoxine/pyrimethamine (SP) is considered an alternative treatment for acute uncomplicated malaria caused by Plasmodium falciparum resistant to chloroquine. However, the appearance of resistance to this drug has been reported since its initial use in Colombia. Molecular analysis of the dihydrofolate reductase gene indicates a correlation between in vitro resistance to SP and the Asn-108 point mutation. Little is known about the association of this point mutation and in vivo resistance to SP. We used a mutation-specific polymerase chain reaction strategy to analyze the presence of the Asn-108 point mutation in 48 clinical samples with adequate clinical response (ACR), 2 early treatment failures (ETF), and 1 late treatment failure (LTF). The Asn-108 mutation was detected in 36 of the ACR samples and in all of the ETF and LTF samples. Eleven ACR samples amplified with the wild-type-specific primer and one amplified with the primer for the Thr-108 mutation described for resistance to cycloguanil. These results suggest that the Asn-108 marker may not be useful in predicting SP treatment failure.

Assessment of therapeutic response of Plasmodium falciparum to chloroquine and sulfadoxine-pyrimethamine in an area of low malaria transmission in Colombia.

Although chloroquine (CQ) resistance was first reported in Colombia in 1961 and sulfadoxine-pyrimethamine (SP) resistance in 1981, the frequency of treatment failures to these drugs in Colombia is unclear. A modified World Health Organization 14-day in vivo drug efficacy test for uncomplicated Plasmodium falciparum malaria in areas with intense malaria transmission was adapted to reflect the clinical and epidemiologic features of a low-intensity malaria transmission area in the Pacific Coast Region of Colombia. Patients > or =1 year of age with a parasite density > or =1,000 asexual parasites per microliter were enrolled in this study. Forty-four percent (24 of 54) of the CQ-treated patients were therapeutic failures, including 7 early treatment failures (ETFs) and 17 late treatment failures (LTFs). Four (6%) of 67 SP-treated patients were therapeutic failures (2 ETFs and 2 LTFs). Therapeutic failure in the CQ-treated group was associated with an age <15 years old (P < 0.01), but was not associated with initial parasite density, the presence of CQ or sulfa-containing drugs in urine, or a history of malaria. The high level of therapeutic failures to CQ detected in this study underscores the need and importance of drug efficacy evaluation in the development of a rational national antimalarial drug policy. The relatively low level of therapeutic failures to SP compared with other South American countries raises further questions regarding factors that might have prevented the rapid development of in vivo resistance to this drug combination.

Mucosal leishmaniasis due to Leishmania (Viannia) panamensis in Colombia: clinical characteristics.

The Leishmaniases are a group of diseases whose clinical presentation is in part determined by the infecting species. Until recently, mucosal leishmaniasis was attributed exclusively to Leishmania (Viannia) braziliensis; however, the capacity of other species of the subgenus Viannia to invade mucosal tissue has been documented. This report examines the clinical characteristics of 23 parasitologically diagnosed patients with mucosal leishmaniasis due to L. (V.) panamensis from the Pacific Coast of Colombia seen at CIDEIM between 1985 and 1996. Most of the mucosal lesions 74% (17 of 23) were mild, with a short time of evolution (median = 2.5 months) and were present concomitantly with an active cutaneous lesion in 61% (14 of 23) of the cases. The simultaneous presentation of mucosal and active cutaneous lesions contrast with classical descriptions of mucosal leishmaniasis caused by L. (V.) braziliensis, and highlights the importance of early diagnosis of mucosal disease by the examination of mucosa in all cases of cutaneous leishmaniasis.